天麻素对阿尔茨海默症大鼠神经保护作用的研究  

Study on neuroprotective effect of gastrodin on rats with Alzheimer’s disease

作　　者：林志川[1] 文国强[1] 吕艳 郑国贤 欧阳锋[1] Lin Zhichuan;Wen Guoqiang;Lü Yan;Zheng Guoxian;Ouyang Feng(Department of Neurology,Hainan General Hospital,Haikou 570311,China)

机构地区：[1]海南省人民医院神经内科,海口570311

出　　处：《广西医科大学学报》2020年第8期1435-1441,共7页Journal of Guangxi Medical University

基　　金：海南省卫计委重点基金资助项目(No.ZDYF2018151);国家自然科学基金资助项目(No.81260204)。

摘　　要：目的:研究天麻素通过调节Wnt信号通路对阿尔茨海默症(AD)大鼠的神经保护作用。方法:将72只大鼠随机分为6组:空白对照组、假手术组、模型组、天麻素高剂量组、天麻素低剂量组、阳性对照组(PC组,0.9 mg/kg盐酸多奈哌齐),每组12只。采用β-淀粉样多肽1-42(Aβ1-42)建立AD大鼠模型。Y迷宫实验检测大鼠的工作记忆能力,Morris水迷宫实验检测大鼠的认知能力,苏木精-伊红(HE)染色检测海马CA1区神经元细胞损伤情况,免疫组织化学检测海马区β-淀粉样蛋白(Aβ)聚集情况,Western blotting检测Wnt信号通路Wnt3a和β-catenin蛋白表达、GSK-3βSer9位点磷酸化水平。结果:与模型组比较,天麻素低剂量组、天麻素高剂量组和PC组大鼠自发交替百分比(SAP)明显升高,第四象限的游泳时间明显延长(P<0.05),逃跑潜伏期明显缩短(P<0.05),神经元细胞形态和神经元细胞数量得到明显改善,Aβ斑块的产生明显减少(P<0.05),Wnt3a、β-catenin蛋白表达和GSK-3βSer9位点磷酸化水平明显升高(P<0.05),且天麻素对AD大鼠的作用呈剂量依赖性。结论:天麻素对Aβ1-42诱导的AD大鼠模型具有神经保护作用,明显改善AD大鼠工作记忆障碍和认知能力,其作用机制可能与Wnt信号通路的激活相关。Objective:To investigate the neuroprotective effect of gastrodin on Alzheimer's disease(AD)ratsby regulating the Wnt signaling pathway.Methods:A total of 72 rats were randomly divided into 6 groups:blank control group,sham operation group,model group,gastrodin high-dose group,gastrodin low-dose group and positive control group(PC group,0.9 mg/kg donepezil hydrochloride),with12 rats in each group.AD rat models were established usingβ-Amyloid 1-42(Aβ1-42).The Y maze test was conducted to detect the working memory ability of rats,the Morris water maze test was used to detect the cognitive ability of rats,hematoxylin-eosin(HE)staining was used to detect neuronal cell damage in hippocampal CA1 area,immunohistochemistry was used to detect hippocampalβ-Amyloid(Aβ)aggregation,and Western blotting was used to detect the expression of Wnt3a andβ-catenin proteins in the Wnt signaling pathway and the phosphorylation of GSK-3βat Ser9.Results:Compared with the model group,the spontaneous alternation percentage(SAP)of rats in the low-dose gastrodin,high-dose gastrodin and PC groups was significantly increased,the swimming time in the fourth quadrant was significantly prolonged(P<0.05),the escape latency was significantly shortened(P<0.05),neuronal cell morphology and neuronal cell number were significantly improved,Aβplaque production was significantly reduced(P<0.05),and Wnt3a,β-catenin protein expressions and phosphorylation of GSK-3βat Ser9 were significantly increased(P<0.05).Besides,the effect of gastrodin on AD rats was dose dependent.Conclusion:Gastrodin has a neuroprotective effect on the AD rat model induced by Aβ1-42.It significantly improves the working memory impairment and cognitive ability of AD rats,and its mechanism may be related to the activation of Wnt signaling pathway.

关 键 词：天麻素 阿尔茨海默症 神经保护 WNT信号通路 

分 类 号：R285.5[医药卫生—中药学]